We are using NIH-approved human embryonic stem cells to generate committed photoreceptors and other retinal cells in vitro. We are generating appropriate fluorescent tags to identify specific stages of retinal neuronal differentiation. Here, the goal is to develop optimal conditions for photoreceptor differentiation and find specific molecular markers for cells that can be used for transplantation. We are also examining the influence of extrinsic and epigenetic signals on retinal differentiation. [unreadable] [unreadable] Another major focus is on investigating the formation of connections between rod and cone cells and their downstream target neurons. We have established novel gene transfer tools in the laboratory to study gene function and directly image neurogenesis in the rodent retina as a model system, with a goal to understand human retinal circuitry. These studies will complement the efforts to engineer stem cells into photoreceptors and functionally integrate these cells into the circuitry of degenerating retinas after transplantation.